TY - JOUR
T1 - Association Between Levels of Sex Hormones and Risk of Esophageal Adenocarcinoma and Barrett's Esophagus
AU - Xie, Shao Hua
AU - Fang, Rui
AU - Huang, Mingtao
AU - Dai, Juncheng
AU - Thrift, Aaron P.
AU - Anderson, Lesley A.
AU - Chow, Wong Ho
AU - Bernstein, Leslie
AU - Gammon, Marilie D.
AU - Risch, Harvey A.
AU - Shaheen, Nicholas J.
AU - Reid, Brian J.
AU - Wu, Anna H.
AU - Iyer, Prasad G.
AU - Liu, Geoffrey
AU - Corley, Douglas A.
AU - Whiteman, David C.
AU - Caldas, Carlos
AU - Pharoah, Paul D.
AU - Hardie, Laura J.
AU - Fitzgerald, Rebecca C.
AU - Shen, Hongbing
AU - Vaughan, Thomas L.
AU - Lagergren, Jesper
N1 - Publisher Copyright:
© 2020 AGA Institute
PY - 2020/11
Y1 - 2020/11
N2 - Background & Aims: Esophageal adenocarcinoma (EAC) occurs most frequently in men. We performed a Mendelian randomization analysis to investigate whether genetic factors that regulate levels of sex hormones are associated with risk of EAC or Barrett's esophagus (BE). Methods: We conducted a Mendelian randomization analysis using data from patients with EAC (n = 2488) or BE (n = 3247) and control participants (n = 2127), included in international consortia of genome-wide association studies in Australia, Europe, and North America. Genetic risk scores or single-nucleotide variants were used as instrumental variables for 9 specific sex hormones. Logistic regression provided odds ratios (ORs) with 95% CIs. Results: Higher genetically predicted levels of follicle-stimulating hormones were associated with increased risks of EAC and/or BE in men (OR, 1.14 per allele increase; 95% CI, 1.01–1.27) and in women (OR, 1.28; 95% CI, 1.03–1.59). Higher predicted levels of luteinizing hormone were associated with a decreased risk of EAC in men (OR, 0.92 per SD increase; 95% CI, 0.87–0.99) and in women (OR, 0.93; 95% CI, 0.79–1.09), and decreased risks of BE (OR, 0.88; 95% CI, 0.77–0.99) and EAC and/or BE (OR, 0.89; 95% CI, 0.79–1.00) in women. We found no clear associations for other hormones studied, including sex hormone–binding globulin, dehydroepiandrosterone sulfate, testosterone, dihydrotestosterone, estradiol, progesterone, or free androgen index. Conclusions: In a Mendelian randomization analysis of data from patients with EAC or BE, we found an association between genetically predicted levels of follicle-stimulating and luteinizing hormones and risk of BE and EAC.
AB - Background & Aims: Esophageal adenocarcinoma (EAC) occurs most frequently in men. We performed a Mendelian randomization analysis to investigate whether genetic factors that regulate levels of sex hormones are associated with risk of EAC or Barrett's esophagus (BE). Methods: We conducted a Mendelian randomization analysis using data from patients with EAC (n = 2488) or BE (n = 3247) and control participants (n = 2127), included in international consortia of genome-wide association studies in Australia, Europe, and North America. Genetic risk scores or single-nucleotide variants were used as instrumental variables for 9 specific sex hormones. Logistic regression provided odds ratios (ORs) with 95% CIs. Results: Higher genetically predicted levels of follicle-stimulating hormones were associated with increased risks of EAC and/or BE in men (OR, 1.14 per allele increase; 95% CI, 1.01–1.27) and in women (OR, 1.28; 95% CI, 1.03–1.59). Higher predicted levels of luteinizing hormone were associated with a decreased risk of EAC in men (OR, 0.92 per SD increase; 95% CI, 0.87–0.99) and in women (OR, 0.93; 95% CI, 0.79–1.09), and decreased risks of BE (OR, 0.88; 95% CI, 0.77–0.99) and EAC and/or BE (OR, 0.89; 95% CI, 0.79–1.00) in women. We found no clear associations for other hormones studied, including sex hormone–binding globulin, dehydroepiandrosterone sulfate, testosterone, dihydrotestosterone, estradiol, progesterone, or free androgen index. Conclusions: In a Mendelian randomization analysis of data from patients with EAC or BE, we found an association between genetically predicted levels of follicle-stimulating and luteinizing hormones and risk of BE and EAC.
KW - Causality
KW - Esophageal Neoplasms
KW - Gonadal Steroid Hormones
KW - Sex Difference
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U2 - 10.1016/j.cgh.2019.11.030
DO - 10.1016/j.cgh.2019.11.030
M3 - Article
C2 - 31756444
AN - SCOPUS:85091221722
SN - 1542-3565
VL - 18
SP - 2701-2709.e3
JO - Clinical Gastroenterology and Hepatology
JF - Clinical Gastroenterology and Hepatology
IS - 12
ER -